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首页> 外文期刊>Journal of Molecular Biology >Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species
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Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species

机译：冠状病毒蛋白质蛋白酶和干扰素刺激基因产物15的结构见解来自不同物种的蛋白酶

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摘要

Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) encode multifunctional papain-like proteases (PLPs) that have the ability to process the viral polyprotein to facilitate RNA replication and antagonize the host innate immune response. The latter function involves reversing the post-translational modification of cellular proteins conjugated with either ubiquitin (Ub) or Ub-like interferon-stimulated gene product 15 (ISG15). Ub is known to be highly conserved among eukaryotes, but surprisingly, ISG15 is highly divergent among animals. The ramifications of this sequence divergence to the recognition of ISG15 by coronavirus PLPs at a structural and biochemical level are poorly understood. Therefore, the activity of PLPs from SARS-CoV, MERS-CoV, and mouse hepatitis virus was evaluated against seven ISG15s originating from an assortment of animal species susceptible, and not, to certain coronavirus infections. Excitingly, our kinetic, thermodynamic, and structural analysis revealed an array of different preferences among PLPs. Included in these studies is the first insight into a coronavirus PLP's interface with ISG15 via SARS-CoV PLpro in complex with the principle binding domain of human ISG15 (hISG15) and mouse ISG15s (mISG15s). The first X-ray structure of the full-length mISG15 protein is also reported and highlights a unique, twisted hinge region of ISG15 that is not conserved in hISG15, suggesting a potential role in differential recognition. Taken together, this new information provides a structural and biochemical understanding of the distinct specificities among coronavirus PLPs observed and addresses a critical gap of how PLPs can interact with ISG15s from a wide variety of species. (C) 2017 Elsevier Ltd. All rights reserved.
机译：严重急性呼吸综合征冠状病毒（SARS-COV）和中东呼吸综合征冠状病毒（MERS-COV）编码具有处理病毒多蛋白的多功能尾皮蛋白酶（PLP），以促进RNA复制并拮抗宿主先天免疫应答。后一函数涉及逆转与泛素（UB）或UB样干扰素刺激的基因产物15（ISG15）缀合的细胞蛋白的翻译后修饰。已知UB在真核生物中受到高度保守，但令人惊讶的是，ISG15在动物中具有高度分歧。在结构和生化水平下，冠状病毒PLP识别该序列分歧的分枝差异很差。因此，评估来自SARS-COV，MERS-COV和小鼠肝炎病毒的PLPS的活性针对源于各种动物物种易感，而不是某些冠状病毒感染的七个ISG15。令人兴奋的是，我们的动力学，热力学和结构分析揭示了PLP之间不同的偏好。这些研究中包含的是通过SARS-COV PLPRO与ISG15的ISG15的界面熟悉，与人ISG15（HISG15）和小鼠ISG15s（MISG15S）的原理结合结构域中复合物。还报道了全长MISG15蛋白的第一X射线结构，并突出了ISG15的独特扭曲铰链区域，其在HISG15中不保守，表明差异识别中的潜在作用。在一起，这种新信息对观察到的冠状病毒PLP中的不同特异性提供了结构和生化理解，并解决了PLPS如何与各种各样的物种与ISG15相互作用的临界差距。 （c）2017 Elsevier Ltd.保留所有权利。

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